Abstract
Impaired wound healing is commonly encountered in patients with diabetes mellitus, which may lead to severe outcomes such as amputation, if untreated timely. Macrophage plays a critical role in the healing process including the resolution phase. Although magnetic therapy is known to improve microcirculation, its effect on wound healing remains uncertain.In the present study, the model of diabetic mice was used to prove the effect of static magnetic field (SMF) in wound healing process. The positive role of SMF in macrophage polarization was observed in wound areas of db/db mice by the immunofluorescence staining and flow cytometric analysis. In order to examine the molecular mechanism of SMF in the wound healing, peritoneal macrophages were isolated from db/db mice and treated by LPS or IL‐4.We found 0.6 T SMF significantly accelerated wound closure rate by 50%. Histological analyses revealed significantly shorter distances by 26.7% between the epithelial tips of punched wound and distances by 33.3% between the edges of the panniculus carnosus in SMF group at day 7 postoperatively. SMF promoted M2 macrophage recruitment by 87.5% and reduced M1 macrophages accumulation by 24.3%, which was observed by immunofluorescence staining in wound areas of db/db mice. Flow cytometry analysis also revealed that M2 macrophages (F4/80+CD206+) were increased and M1 macrophages (F4/80+CD206−) were significantly decreased, indicating SMF facilitates M2 polarization in inflamed tissues. The expression levels of pro‐inflammatory markers (iNOS, IL‐6, IL‐1β, CCR7) in injured tissues were paradoxically downregulated in the SMF group. Meanwhile, SMF significantly raised the expression levels of reparative genes (CD206, Fizz1, Arg‐1, IL‐10). The pro‐inflammatory iNOS expression was decreased and anti‐inflammatory Arg‐1 was increased in SMF/LPS/IL‐4‐treated macrophages. Furthermore, SMF inhibited LPS‐induced STAT1 phosphorylation and augmented IL‐4‐induced STAT6 phosphorylation in the macrophages.In summary, our study showed for the first time the effect of 0.6 T SMF on wound healing in diabetic mice. These results indicate that SMF accelerates diabetic wound healing by promoting macrophage polarization and resolution of inflammation through modulation of the JAK‐STAT pathway. Therefore, focusing on SMF in therapeutic interventions might be useful for treating diabetic wound by re‐normalizing the healing process.Support or Funding InformationThis work was supported by the National Natural Science Foundation of China (grants 81703591).
Highlights
The diabetic foot ulcer is one of the most common and severe complications of diabetes mellitus because of impaired wound healing [1, 2]
To investigate the therapeutic effect of Static magnetic field (SMF) on diabetic injury, the db/db mice were housed in a 230 mm × 130 mm × 15 mm plate with 24 magnetic pieces (0.6 T) embedded (Figure 1(a))
Wound healing is frequently impaired in patients with diabetes mellitus, and its treatment is still a big challenge
Summary
The diabetic foot ulcer is one of the most common and severe complications of diabetes mellitus because of impaired wound healing [1, 2]. The standard treatment for diabetic wounds includes debridement of the wound, treatment of any infection, revascularization, and off-loading of the ulcer [4] Several strategies, such as the wound healing peptides, have been used with high efficiency [5, 6], some refractory wounds and high costs of wound care predispose the patients to delay the treatment. It is desirable to explore alternative and cost-effective therapies for the patients with severe diabetic wounds. Studies have shown that SMF may influence the production of inflammatory cytokines released by macrophages and lymphocytes [14]. The therapeutic effect of SMF on diabetic wound healing remains to be determined. We observed that SMF significantly accelerated wound closure and revascularization by driving macrophages towards M2 polarization and inflammatory resolution through balancing STAT1/STAT6 signaling. The results suggest that SMF may serve as an effective therapeutic approach for diabetic wound
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